A meibomian gland is a lipid-producing gland included in the upper and lower eyelids, and secretes a lipid through an opening situated on a conjunctival side from eyelashes of eyelids. A lipid layer constituting a tear fluid contains a lipid supplied from the meibomian gland as a component, and prevents the tear fluid from evaporating from an eye surface. It is known that, in a meibomian gland dysfunction or meibomitis patient, the function of the meibomian gland is deteriorated, and a secretion amount of a lipid is decreased, causing hyperevaporative dry eye, a keratoconjunctival epithelial disorder, corneal epithelial erosion and corneal ulcer, which are associated with dry eye, and the like.
In addition, a cornea consists of an ectodermal epithelium and a mesodermal anterior limiting layer (Bowman's membrane)/stroma/posterior limiting layer (Descemet's membrane)/endothelium. Since the cornea is the frontmost part of eyeballs, it easily undergoes the influence of the external environment and, as a result, various disorders are generated. Examples of a disease associated with a damage or a defect of a corneal epithelial cell include dry eye syndrome, corneal ulcer, superficial punctate keratitis, corneal epithelial erosion, ocular allergic diseases associated with a corneal lesion such as spring catarrh and atopic keratoconjunctivitis, and the like.
On the other hand, PPAR is one of intranuclear receptors, which is expressed in almost all vertebrates, and is said to be a transcription factor group closely involved in intracellular saccharide-lipid metabolism and differentiation of a cell. As a subtype, α, δ and γ are known. A PPARδ is termed as PPARβ in some cases (Non-Patent Literature 1).
As the distribution of PPAR in an ocular tissue, it is known that PPARα and β are expressed in a corneal epithelial cell of a rabbit (Non-Patent Literature 2).
Previously, it has been reported that 5-[4-(6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy)benzyl]thiazolidine-2,4-dione having a PPAR activating action can be utilized as an agent for treating a keratoconjunctival disorder (Patent Literatures 1 and 2), and a PPARα, δ or γ agonist is administered in treating an ocular disease (conjunctivitis, dry eye syndrome, corneitis, or the like) (Patent Literature 3). In addition, PPARα is known to be distributed in the liver, kidney and the like and to act on lipid metabolism/transportation and, further, it has been reported that an agonist thereof can be utilized as an agent for treating a corneal disease (Patent Literature 4). With respect to a PPARδ agonist, it has previously been reported that the agonist promotes proliferation and differentiation of a rat sebaceous gland epithelial cell (Non-Patent Literature 3), and promotes healing of skin injury (Non-Patent Literature 4). Additionally, a method of stimulating proliferation of a β-cell by administering a non-thiazolidinedione PPAR ligand and a GLP-1 derivative (Patent Literature 5), and inhibition of proliferation of a leukemia cell and a prostate cancer cell by pioglitazone which is a PPARγ agonist (Patent Literature 6) are known.
However, the expression and function of PPARα, δ and γ in each animal species and each tissue or cell contain many questions to be answered, and which PPAR agonist is useful for human ocular diseases is not known.    [Patent Literature 1] WO 2005/039574    [Patent Literature 2] Japanese Patent Application Laid-Open (JP-A) No. 2001-39976    [Patent Literature 3] WO 2002/076177    [Patent Literature 4] JP-A No. 2005-008570    [Patent Literature 5] WO 2002/69994    [Patent Literature 6] WO 1998/25598    [Non-Patent Literature 1] J Med Chem 2000, 43: 527-550    [Non-Patent Literature 2] J Biol Chem 2000, 275: 2837    [Non-Patent Literature 3] Molecular Genetic and Metabolism 2001, 74: 362-369    [Non-Patent Literature 4] Am J Clin Dermatol 2003, 4(8): 523-530